Many natural compounds that bear a guanidine function have biological activity that make them useful as pharmaceuticals. Among these compounds are antimicrobials, antifungals, antivirals, neurotoxins, hormones, and agents that act as agonists or antagonists to biological signals. A review of these natural products is presented in Progress in the Chemistry of Organic Natural Products (1995) 66:119 and Berlinck, R. G. S. (1996) Nat. Prod. Reports 13(5):377-409. Much effort has been directed to developing routes for preparing these compounds or their analogues synthetically.
Guanidine-containing bioactive molecules, particularly the analogs or derivatives of the natural products, are now significant targets for drug design and discovery. The guanidine moiety in the bioactive compound frequently occurs in arginine-containing polypeptide chains which may comprise the entire biomolecule or exist as an incorporated moiety. Arginine, together with lysine, another amino acid with a positively charged side chain, plays an important role in biologically active proteins and peptides. Various arginine analogues and derivatives have been synthesized and incorporated into peptides and peptidomimetics to study the structure-activity relationships of arginine-containing molecules. These residues are frequently the critical amino acid residues in peptidomimetics.
A completely satisfactory guanidinylating reagent has not yet been achieved. More effective guanidinylation reagents are useful in improving the synthesis of arginine analogues and other guanidine-containing molecules.